Endocrine Abstracts

Single gene defects causing severe insulin resistance have been elucidated either by directed screening of candidate genes (INSR, AKT2, PPARG) or by detailed linkage mapping in large pedigrees (BSCL2, AGPAT2, LMNA), and study of patients harbouring these known defects continues to yield important insights into insulin’s action in health and disease. However a large proportion of the genetic defects leading to severe insulin resistance in slim subjects remains undiscovered...

Leptin and adiponectin are cytokine-like hormones secreted by white adipose tissue. Plasma leptin correlates closely with total body fat mass, and its secretion is positively regulated by insulin in vivo and in vitro. Hypoleptinaemia is a key centrally-mediated orexigenic stimulus. Plasma adiponectin, in contrast, correlates negatively with whole body fat mass and insulin resistance in adults, and its expression is regulated negatively by insulin in vivo a...

Objectives: Insulin resistance (IR) and obesity are very common metabolic abnormalities, which are often associated with reduced GH secretion. GH reduces intraabdominal fat and its deficiency may contribute to the metabolic syndrome. IGF-1 improves IR but IGFBPs have a potential role in regulating its bioactivity although only little information exists. We postulate that the elevated insulin levels in IR may persistently suppress GH provided its regulation remains insulin sens...

Objective: The mechanisms underlying the well known glucagon-induced satiety effect are unclear. We showed earlier that glucagon induces a remarkable decrease in the orexigenic hormone: ghrelin. It was the aim of the present study to further evaluate the effect of glucagon on ghrelin secretion and the possible site of origin of this effect.Methods: We studied the endocrine and metabolic responses to intramuscular glucagon administration in 23 subjects (1...

Mutation of the GPR54 receptor is associated with a failure of reproductive function. The endogenous neuropeptide agonist for GPR54, kisspeptin, potently stimulates the hypothalamic-pituitary-gonadal (HPG) axis in rodents and primates.Objective: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH and testosterone in male volunteers.Method: Study (i) Volunteers were infused w...

Kisspeptin is a 54 amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates the G-protein-coupled receptor, GPR54. The kisspeptin/GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy but levels in gestational trophoblastic neoplasia (GTN) have not previously been reported. The...

RAP (LDL receptor associated protein) is a 44 kDa endoplasmic reticulum (ER) resident molecular chaperone. In the thyroid RAP is required for expression of megalin, an endocytic receptor responsible for transcytosis of thyroglobulin (Tg), but it also binds to Tg itself, suggesting it may affect thyroid function in various manners. Indeed, findings in RAP KO mice indicate that disruption of the RAP gene results in impaired Tg storage into the colloid, suggesting that RAP serves...

Introduction: Ghrelin is an orexigenic hormone with two isoforms: Acyl Ghrelin (AG) and Desacyl Ghrelin (DAG). AG binds to its specific receptor GHS-R1 and stimulates growth hormone secretion. DAG also binds to GHS-R1 receptor, but with 1000 times less affinity than AG. Effect of DAG on cell proliferation and inhibition of apoptosis has been reported. However, there are no studies of DAG function in human placenta. For first time, this work analyzed the effect of DAG on viabil...

Background: Transpersons can receive gender affirming hormone therapy (HT) to induce physical changes. Little is known about the effect of HT on breast cancer (BC) risk.Objectives: To study the prevalence and characteristics of BC in transpersons with HT and to compare this prevalence with the general Dutch male and female population.Methods: Adult transpersons who were seen after 1991 and started HT in the VUmc were included. This...

Introduction: Joubert Syndrome (JS) is a rare ciliopathy condition, presenting distinctive cerebellar and brain stem malformation called the “molar tooth sign” (MTS) on brain imaging. Patients suffer from neonatal breathing dysregulation, developmental delay, hypotonia, abnormal eye movements. Endocrine disorders are only rarely evaluated, to date only few reports highlight the importance of hormonal evaluation.Material...